Korean J Physiol Pharmacol.  2006 Jun;10(3):149-154.

Effects of Phosphodiesterase 5 Inhibition with Sildenafil on Atrial Contractile and Secretory Function

• Quan HX
• Kim SY
• Jin XS
• Park JK
• Kim SZ
• Cho KW

Abstract

Selective inhibition of phosphodiesterase (PDE) 5 opened a new therapeutic approach for cardiovascular disorders. Therefore, the effect of PDE5 inhibition on the cardiac function should thoroughly be defined. The purpose of the present study was to define the effects of sildenafil, a selective inhibitor of PDE5, on the atrial cGMP efflux, atrial dynamics, and the release of atrial natriuretic peptide (ANP). By perfusing rabbit left atria to allow atrial pacing, changes in atrial stroke volume and pulse pressure, transmural extracellular fluid translocation, cGMP efflux, and ANP secretion were measured. SIN-1, an NO donor and soluble (s) guanylyl cyclase (GC) activator, and C-type natriuretic peptide (CNP), an activator of particulate (p) GC activator, were used. Sildenafil increased basal levels of cGMP efflux slightly but not significantly. Sildenafil in a therapeutic dose increased atrial dynamics (for atrial stroke volume, 2.84+/-1.71%, n=12, vs -0.71+/-0.86%, n=21; p<0.05) and decreased ANP release (-9.02+/-3.36%, n=14, vs 1.35+/-3.25%, n=23; p<0.05), however, it had no effect on the SIN-1- or CNP-induced increase of cGMP levels. Furthermore, sildenafil in a therapeutic dose accentuated SIN-1-induced, but not CNP-induced, decrease of atrial pulse pressure and ANP release. These data indicate that PDE5 inhibition with sildenafil has a minor effect on cGMP levels, but has a distinct effect on pGC-cGMP- and sGC-cGMP-induced contractile and secretory function.

Keyword

Atrial natriuretic peptide; Atrium; cGMP; Phosphodiesterase 5; Sildenafil

MeSH Terms

Atrial Natriuretic Factor
Blood Pressure
Cyclic Nucleotide Phosphodiesterases, Type 5*
Extracellular Fluid
Guanylate Cyclase
Humans
Natriuretic Peptide, C-Type
Stroke Volume
Tissue Donors
Sildenafil Citrate
Atrial Natriuretic Factor
Cyclic Nucleotide Phosphodiesterases, Type 5
Guanylate Cyclase
Natriuretic Peptide, C-Type